Hitherto, a polymer material has been widely utilized in a sustained-release pharmaceutical composition because it allows a concentration of a drug in a tissue to be effectively retained over a long period. The polymer material has such characteristics that the material can bind a drug in a physical or chemical manner and releases the drug along with progression of its in vivo degradation. Such polymer material is exemplified by a cellulose derivative, a starch derivative, a dextran derivative, a polysaccharide, a protein, a polypeptide, an acrylic acid derivative, or a vinyl derivative.
As a sustained-release characteristic of a drug mediated by a collagen as the protein, it is known that a sustained-release period of a drug can be controlled to a short period (about several days) to a long period (several months) by regulating a collagen concentration. For example, Patent Literature 1 discloses that when the collagen concentration is reduced, degradation of a gelated collagen containing a drug is accelerated, sustained release of the drug is also accelerated, and thus a drug efficacy period is completed within a short period, and in contrast, that when the collagen concentration is increased, degradation of a gelated collagen is delayed, sustained release of the drug is also delayed, and thus drug efficacy can be exhibited for a long period. However, when the collagen concentration is high, a sophisticated technology is required because of difficulty in formulation. Further, in contrast, when the collagen concentration is low, although operations such as injection into a tissue and addition and mixing of a drug become easy, there is a problem, for example, in that a drug sustained-release rate after injection into a tissue becomes high, drug efficacy is exhibited within only a short period, and sustained-release for a long period is not attained, with the result that drug efficacy is not sufficiently obtained.
Patent Literature 2 discloses a local sustained-release formulation for wound healing promotion obtained by mixing a carrier containing a collagen as an essential constituent with a physiologically active substance having a wound healing promoting activity. The carrier described in Patent Literature 2 is constructed of ingredients selected from the group consisting of proteins such as a collagen and an albumin, carbohydrates such as a chitin, and synthetic polymers. Patent Literature 2 discloses that a sustained-release characteristic of a drug depends on dosage forms such as a powder and a film. However, it takes much time to form the formulation into any of those dosage forms, and thus the formulation is lack of convenience. Further, Patent Literature 3 discloses a sustained-release formulation containing a collagen, a glycosaminoglycan as a polysaccharide, and a drug. Patent Literature 3 discloses that the glycosaminoglycan controls fibrillogenesis of the collagen and functions as a release control factor for the drug. The sustained-release formulation of Patent Literature 3 is a solid formulation, is formed into a dosage form such as a needle or a stick, and hence is lack of convenience as with the formulation described in Patent Literature 2.
It is known that a collagen solution undergoes gelation when heated to around a body temperature in vitro, and it is also known that addition of a sugar such as a monosaccharide or a disaccharide to a collagen solution in advance inhibits gelation of the solution (Non Patent Literature 1 and Non Patent Literature 2). Ina state in which the gelation is inhibited, it is considered that a sustained-release characteristic of a drug mediated by a collagen is not sufficiently exhibited. Hence, in applying the collagen as a carrier for a sustained-release pharmaceutical, it has been impossible to employ a technology for inhibiting gelation using the collagen in combination with a sugar such as a monosaccharide.